Various medicament (drug) solutions are commonly administered intravenously (via IV) from sterile containers to patients. Oftentimes, such solutions comprise a mixed combination of a liquid diluent, e.g., an aqueous dextrose or NaCl solution, and a medicament. Desirably, the medicament and diluent are stored separately in the container under aseptic conditions and are not mixed together until immediately prior to use so as to prevent degradation of the final product. Common packaging of the diluent and medicament is complicated by the nature of the medicament, which is often a powder which is sensitive to moisture contamination, or a powder or liquid sensitive to degradation under light or oxygen exposure.
Various multiple compartment containers have been disclosed which are used for aseptic storage and mixing of diluents and medicaments. For example, such containers are disclosed in U.S. Pat. No. 4,608,043 (Larkin) and U.S. Pat. No. 5,176,634 (Smith et al). U.S. Pat. Nos. 4,608,043 and 5,176,634 are incorporated herein in their entirety by this reference. The compartments of the containers disclosed in the foregoing patents are separated from each other by frangible heat seals. The seals are ruptured by manipulation of the container so that the contents of the compartments can be mixed together to thereby form a solution which is delivered to the patient through a standard IV arrangement.
The design of the containers of the '043 and '634 patents results in the sterilization process being more complex and, thus, more expensive than it needs to be. The complications with the sterilization process arise, in part, because of the Federal Food and Drug Administration (FDA) requirement that a level of sterility be achieved which is at least as high as the level achieved by the current practice of terminal steam sterilization. Achieving this high level of sterility is not possible with current aseptic liquid-fill technology. Therefore, to meet the FDA requirement, after a container has been filled with a liquid and sealed, it must be sterilized, i.e., it must undergo a terminal or final sterilization procedure.
Thus, the containers disclosed in the '043 and '634 patents must be sterilized either (1) after both the powdered medicament and diluent are in place in their respective sealed compartments or (2) after the diluent is in its sealed compartment while the medicament compartment remains empty. Both such processes present difficulties. In the first process, the container is fabricated with the diluent and medicament compartments unfilled and open for receiving the diluent and the medicament, respectively. The container is then sterilized, e.g., by radiation, and the diluent and medicament are aseptically filled into the two sterilized compartments and the compartments are sealed. Because of the aforementioned FDA requirement, the container and its contents must then be sterilized again, i.e., the container must undergo a final or terminal sterilization. One form of such final sterilization is to use steam in an autoclave process. Because powdered medicaments can be degraded to some degree by moisture or heat, the use of steam for final sterilization is not optimum. Furthermore, because such containers use film materials which are designed to protect powdered medicaments from moisture and atmospheric gases, it takes longer for steam to penetrate the film to provide its sterilization function, resulting in process inefficiencies.
Although such containers with a diluent sealed therein could undergo final sterilization with radiation, several problems are encountered with such a process. Firstly, dextrose diluents are degraded by radiation. Secondly, when aqueous solutions are irradiated, undesirable peroxides can be formed. The use of ethylene oxide (EtO) instead of radiation for final sterilization is not possible because the EtO gas will not effectively penetrate the films from which the containers are constructed. Thus, neither radiation nor EtO sterilization can be used to eliminate the problems which are described above as being associated with the autoclave process.
If final sterilization of the containers of the '634 and '043 patents is done after the diluent is in its respective compartment, but before the powdered medicament is in place, other problems may result. For example, if the container is steam sterilized (autoclaved) with the medicament compartment empty, moisture can become entrapped in the medicament compartment and/or within the film structure. Because such moisture can damage the medicament which is to be filled into the compartment, the compartment should be dried before the medicament is placed therein. This results in extra processing steps and additional expense. Furthermore, the same problems which are described above, with regard to sterilizing the container using radiation or EtO, are present if such radiation or EtO were to be used as a sterilization step for a container which contains a diluent in the absence of a medicament.
In view of the foregoing, it can be seen that there is a need for a sterile medicament container which is designed to eliminate the requirement that it undergo final sterilization after a liquid diluent is sealed in place therein.